Lisinopril/hydrochlorothiazide: Side Effects and More

Highlights for hydrochlorothiazide-lisinopril

1. Lisinopril/hydrochlorothiazide oral tablet is available as a brand-name drug and a generic drug. Brand name: Zestoretic.
2. Lisinopril/hydrochlorothiazide only comes as a tablet you take by mouth.
3. Lisinopril/hydrochlorothiazide oral tablet is used to treat hypertension (high blood pressure).

FDA warning: Use during pregnancy

• This drug has a black box warning. This is the most serious warning from the Food and Drug Administration (FDA). A black box warning alerts doctors and patients about drug effects that may be dangerous.
• You shouldn’t take this drug during pregnancy. This drug can harm or end your pregnancy. If you become pregnant, call your doctor and stop taking this drug right away.

Was this helpful?

Other warnings

• Allergic reaction warning: This drug can cause allergic reactions. Some of these reactions can be severe. These include head and neck swelling, trouble breathing, and severe stomach pain.
• Low blood pressure warning: This drug can cause very low blood pressure. Tell your doctor if you have signs of low blood pressure, such as dizziness or feeling like you might faint.
• Liver failure warning: This drug can rarely cause a syndrome that starts as jaundice (yellowing of your skin or the whites of your eyes) and progresses to severe liver damage. If you develop jaundice or have tests that show that your liver enzymes have increased, your doctor will tell you to stop taking this drug.

Lisinopril/hydrochlorothiazide is a prescription drug. It comes as an oral tablet.

Lisinopril/hydrochlorothiazide is available as the brand-name drug Zestoretic. It’s also available as a generic drug. Generic drugs usually cost less than the brand-name version. In some cases, they may not be available in every strength or form as the brand-name drug.

Lisinopril/hydrochlorothiazide is a combination of two drugs in a single form. It’s important to know about all the drugs in the combination because each drug may affect you in a different way.

Lisinopril/hydrochlorothiazide may be taken in combination with beta-blockers, angiotensin receptor blockers, calcium channel blockers, and diuretics to treat high blood pressure. It’s usually given when one medication isn’t enough to control your blood pressure.

How it works

Lisinopril belongs to a class of drugs called angiotensin-converting enzyme (ACE) inhibitors. Hydrochlorothiazide belongs to a class of drugs called diuretics (water pills). A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.

It’s thought that hydrochlorothiazide works to remove excess salt and water from your body. This keeps your heart from working as hard to pump blood. This lowers your blood pressure.

Lisinopril relaxes the blood vessels in your body. This reduces stress on your heart and lowers your blood pressure.

Hydrochlorothiazide-lisinopril oral tablet doesn’t cause drowsiness, but it can cause other side effects.

More common side effects

The more common side effects that can occur with lisinopril/hydrochlorothiazide include:

• dizziness
• headache
• persistent cough
• fatigue
• low blood pressure, especially when you stand up after sitting or lying down

If these effects are mild, they may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist.

Serious side effects

Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

• Serious allergic reactions. Symptoms can include:
• swelling of your head, neck, or lips
• stomach pain
• Low blood pressure. Symptoms can include:
• dizziness
• fainting
• Liver failure. Symptoms can include:
• yellowing of your skin or the whites of your eyes
• increased liver enzymes (shown in a test your doctor will do)
• fatigue
• stomach pain
• nausea and vomiting

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we can not guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare provider who knows your medical history.

Lisinopril/hydrochlorothiazide oral tablet can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Examples of drugs that can cause interactions with lisinopril/hydrochlorothiazide are listed below.

Barbiturates and narcotics

Taking certain barbiturates and narcotics with lisinopril/hydrochlorothiazide may increase your risk of low blood pressure when standing up after sitting or lying down. Examples of these drugs include:

• phenobarbital
• morphine
• fentanyl
• hydrocodone

Blood pressure drugs

Taking other drugs that reduce blood pressure with lisinopril/hydrochlorothiazide may cause your blood pressure to drop too low. This can cause dizziness, headache, or fatigue. Examples of these drugs include:

• angiotensin receptor blockers (ARBs), such as:
• losartan
• valsartan
• olmesartan
• candesartan
• angiotensin-converting enzyme (ACE) inhibitors, such as:
• benazepril
• captopril
• enalapril
• lisinopril
• direct renin inhibitors, such as:
• aliskiren. Don’t take aliskiren with this drug if you have diabetes or kidney problems.

In addition, lisinopril/hydrochlorothiazide interacts with other blood pressure drugs that increase your potassium levels. Your doctor may check your potassium level with blood tests. Examples of these drugs include:

• potassium-sparing diuretics, such as:
• spironolactone
• amiloride
• triamterene

Cholesterol drugs

Taking lisinopril/hydrochlorothiazide with certain drugs used to lower cholesterol levels can reduce the amount of lisinopril/hydrochlorothiazide that your body absorbs. This means that it may not work as well to treat your blood pressure.

Examples of these drugs include:

• cholestyramine
• colestipol

Corticosteroids and adrenocorticotropic hormones

Taking these drugs with lisinopril/hydrochlorothiazide may cause low levels of electrolytes.

Diabetes drugs

Taking certain diabetes drugs with lisinopril/hydrochlorothiazide may affect your blood sugar levels. If you take lisinopril/hydrochlorothiazide with one of these drugs, your doctor may change the dosage of that diabetes drug.

Examples of these drugs include:

• metformin
• glyburide
• glipizide
• insulin

Injectable gold

Taking lisinopril/hydrochlorothiazide with injectable gold may cause flushing (reddening and warming of your face), stomach problems, low blood pressure, dizziness, and a fast heart rate.

Lithium

Taking lisinopril/hydrochlorothiazide with lithium can cause lithium toxicity. This may cause confusion, increased urination, thirst, or an irregular heart rate.

Pain drugs

Taking certain pain drugs with lisinopril/hydrochlorothiazide may decrease your kidney function. This can cause swelling in your legs or problems with urination. Examples of these drugs include:

• diclofenac
• indomethacin
• ketoprofen
• ketorolac
• sulindac
• flurbiprofen

Sacubitril

You should not use lisinopril/hydrochlorothiazide within 36 hours of using sacubitril. Sacubitril is used with valsartan to treat high blood pressure and heart failure. Taking sacubitril with lisinopril/hydrochlorothiazide raises your risk of angioedema (serious swelling).

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we can not guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

This drug comes with several warnings.

Allergy warning

This drug can cause a severe allergic reaction. Symptoms include:

• trouble breathing
• swelling of your throat or tongue
• hives
• severe stomach pain

If you develop these symptoms, call 911 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it or any angiotensin-converting enzyme inhibitors, diuretics, or sulfonamide drugs. Taking it again could be fatal (cause death).

Alcohol interaction warning

The use of drinks that contain alcohol can increase your risk of a side effect from lisinopril/hydrochlorothiazide. This side effect is low blood pressure when you stand up after sitting or lying down, which can cause dizziness. If you drink alcohol, talk to your doctor.

Warnings for people with certain health conditions

For people with diabetes: This drug can affect your blood sugar levels. Your doctor may need to change your dosage of your diabetes medications.

For people with certain heart problems: This drug may lower your blood pressure too much if you have aortic stenosis or hypertrophic cardiomyopathy.

For people with poor kidney function: This drug can further reduce your kidney function. Talk to your doctor about whether this drug is safe for you.

For people with high potassium levels: This drug may increase your potassium levels more. This is often temporary, but may lead to serious heart rate problems.

For people with a cough: This drug may cause a persistent cough or make your cough worse. This cough usually goes away when you stop taking this drug.

Warnings for other groups

For pregnant women: During the first trimester, this drug is a category C pregnancy drug. That means two things:

1. Research in humans has shown adverse effects to the fetus when the mother takes the drug.
2. This drug should only be used during pregnancy in serious cases where it’s needed to treat a dangerous condition in the mother.

Talk to your doctor if you’re pregnant or planning to become pregnant. Ask your doctor to tell you about the specific harm that may be done to your pregnancy. This drug should only be used if the potential risk is acceptable given the drug’s potential benefit.

If you become pregnant while taking this drug, call your doctor right away.

For women who are breastfeeding: This drug may pass into breast milk and may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this medication.

For seniors: Older adults may process drugs more slowly. A typical adult dosage may cause levels of this drug to be higher than normal in your body. If you’re a senior, you may need a lower dosage or a different dosing schedule.

For children: This drug hasn’t been studied in children. It shouldn’t be used in children under the age of 18 years.

All possible dosages and forms may not be included here. Your dose, form, and how often you take it will depend on:

• your age
• the condition being treated
• how severe your condition is
• other medical conditions you have
• how you react to the first dose

Drug forms and strengths

Generic: Lisinopril/hydrochlorothiazide

• Form: oral tablet
• Strengths:
• 10 mg lisinopril/12. 5 mg hydrochlorothiazide
• 20 mg lisinopril/12.5 mg hydrochlorothiazide
• 20 mg lisinopril/25 mg hydrochlorothiazide

Brand: Zestoretic

• Form: oral tablet
• Strengths:
• 10 mg lisinopril/12.5 mg hydrochlorothiazide
• 20 mg lisinopril/12.5 mg hydrochlorothiazide
• 20 mg lisinopril/25 mg hydrochlorothiazide

Dosage for hypertension (high blood pressure)

Adult dosage (ages 18–64 years)

• Typical starting dosage: 10–20 mg lisinopril/12.5 mg hydrochlorothiazide taken once per day.
• Dosage increases: Your doctor will increase your dosage as needed. They may increase your dosage after 2–3 weeks of treatment.

Child dosage (ages 0–17 years)

This drug hasn’t been studied in children. It shouldn’t be used in children under the age of 18 years.

Senior dosage (ages 65 years and older)

• There are no specific recommendations for senior dosing. Older adults may process drugs more slowly. A typical adult dosage may cause levels of this drug to be higher than normal in your body. If you’re a senior, you may need a lower dosage or a different dosing schedule.
• Your doctor may increase your dosage after 2–3 weeks of treatment.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we can not guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always speak with your doctor or pharmacist about dosages that are right for you.

Hydrochlorothiazide-lisinopril oral tablet is used for long-term treatment. This drug comes with serious risks if you don’t take it as prescribed.

If you don’t take it at all: Your blood pressure may increase. This can lead to a heart attack or a stroke.

If you stop taking it suddenly: Your blood pressure may increase.

If you don’t take it on schedule: You may still have high blood pressure. Or you may have more side effects because a consistent level of the drug isn’t in your body. This drug may stop working for you and you may need to use another blood pressure medication.

What to do if you miss a dose: If you forget to take your dose, take it as soon as you remember. If it’s just a few hours until the time for your next dose, then wait and only take one dose at that time.

Never try to catch up by taking two doses at once. This could result in dangerous side effects.

If you take too much: You may have some of the side effects of this drug. These include:

• low blood pressure
• dizziness
• fainting

If you think you’ve taken too much of this drug, call your doctor or local poison control center. If your symptoms are severe, call 911 or go to the nearest emergency room right away.

How to tell if the drug is working: Your doctor will check your blood pressure to tell if this drug is working for you. Your doctor may also ask you to check your blood pressure at home.

Keep these considerations in mind if your doctor prescribes hydrochlorothiazide-lisinopril for you.

General

• This drug can be taken with or without food.
• Take this drug at the same time each day.
• Don’t crush or cut the tablet.

Storage

• Store this drug at a temperature between 68°F and 77°F (20°C and 25°C).
• Keep this drug away from light.
• Don’t store this medication in moist or damp areas, such as bathrooms.

Refills

A prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.

Travel

When traveling with your medication:

• Always carry your medication with you, such as in your carry-on bag.
• Don’t worry about airport X-ray machines. They can’t harm your medication.
• You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled container with you.
• Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.

Self-management

You may need to check your blood pressure at home. You should keep a log with the date, time of day, and your blood pressure readings. Bring this diary with you to your doctor appointments.

To check your blood pressure, you may need to buy a blood pressure monitor. These are available at most pharmacies.

Clinical monitoring

While you’re being treated with this drug, your doctor may check your:

• blood pressure
• kidney function
• electrolyte levels

Your diet

Your diet may affect how well your high blood pressure is controlled. Ask your doctor if you should make changes to your diet.

There are other drugs available to treat your condition. Some may be better suited for you than others. Talk to your doctor about other drug options that may work for you.

Disclaimer: Healthline has made every effort to make certain that all information is factually correct, comprehensive, and up-to-date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or other healthcare professional before taking any medication. The drug information contained here in is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

Mylan-Lisinopril HCTZ – Uses, Side Effects, Interactions

How does this medication work? What will it do for me?

This is a combination product containing 2 medications: lisinopril and hydrochlorothiazide. It is used to treat high blood pressure.

Lisinopril belongs to a class of medications called ACE inhibitors and helps to lower blood pressure by relaxing blood vessels and reducing the workload of the heart. Hydrochlorothiazide belongs to a class of medications called diuretics or “water pills” that help control blood pressure by getting rid of excess salt and water.

It may take up to 2 to 4 weeks to see the full benefits of the medication.

This medication may be available under multiple brand names and/or in several different forms. Any specific brand name of this medication may not be available in all of the forms or approved for all of the conditions discussed here. As well, some forms of this medication may not be used for all of the conditions discussed here.

Your doctor may have suggested this medication for conditions other than those listed in these drug information articles. If you have not discussed this with your doctor or are not sure why you are taking this medication, speak to your doctor.  Do not stop taking this medication without consulting your doctor.

Do not give this medication to anyone else, even if they have the same symptoms as you do. It can be harmful for people to take this medication if their doctor has not prescribed it.

What form(s) does this medication come in?

Mylan-Lisinopril HCTZ is no longer being manufactured for sale in Canada. For brands that may still be available, search under lisinopril – hydrochlorothiazide. This article is being kept available for reference purposes only. If you are using this medication, speak with your doctor or pharmacist for information about your treatment options.

How should I use this medication?

Lisinopril – hydrochlorothiazide is not intended to be used to start treatment of high blood pressure. Each medication should be taken as a separate tablet until the appropriate dose of each medication is determined. Once the dose of each medication (lisinopril and hydrochlorothiazide) that best controls your blood pressure has been determined, the combination tablets can be started.

The recommended dose ranges are:

• lisinopril 10 mg – hydrochlorothiazide 12.5 mg, 1 tablet once daily
• lisinopril 20 mg – hydrochlorothiazide 12.5 mg, 1 or 2 tablets once daily
• lisinopril 20 mg – hydrochlorothiazide 25 mg, 1 or 2 tablets once daily

This medication can be taken with or without food. Swallow the tablet with water. Try to take your tablet at the same time each day, preferably in the morning.

Lower doses may be used for people who take other medications that lower blood pressure or for people who have kidney disease.

Do not stop taking your tablets unless your doctor recommends it.

Many things can affect the dose of medication that a person needs, such as their body weight, other medical conditions, and other medications. If your doctor has recommended a dose different from the ones given here, do not change the way that you are taking the medication without consulting your doctor.

It is important that this medication be taken exactly as prescribed by your doctor. If you miss a dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. If you are not sure what to do after missing a dose, contact your doctor or pharmacist for advice.

Store this medication at room temperature, protect it from light and moisture, and keep it out of the reach of children.

Do not dispose of medications in wastewater (e.g. down the sink or in the toilet) or in household garbage. Ask your pharmacist how to dispose of medications that are no longer needed or have expired.

Who should NOT take this medication?

Do not take this medication if you:

• are allergic to lisinopril, hydrochlorothiazide, or any ingredients of this medication
• are allergic to other angiotensin-converting enzyme inhibitors
• are allergic to sulfa (sulfonamide) medications
• are pregnant or intend to become pregnant
• are breast-feeding
• have difficulty producing urine or are unable to urinate
• have a history of angioedema after taking any ACE inhibitors (e. g., captopril, enalapril, fosinopril, lisinopril, ramipril)
• are taking aliskiren and have congestive heart failure with low blood pressure
• have hereditary angioedema (a serious allergic reaction which causes swelling of the hands, feet, ankles, face, lips, tongue, or throat) or have angioedema with no known cause
• have diabetes, kidney disease, congestive heart failure with low blood pressure, or high levels of potassium in the blood and are taking aliskiren
• are taking sacubitril/valsartan
• are taking other angiotensin converting enzyme inhibitors or angiotensin receptor blockers and have advanced diabetes, kidney disease, congestive heart failure with low blood pressure or high levels of potassium in the blood

What side effects are possible with this medication?

Many medications can cause side effects. A side effect is an unwanted response to a medication when it is taken in normal doses. Side effects can be mild or severe, temporary or permanent.

The side effects listed below are not experienced by everyone who takes this medication. If you are concerned about side effects, discuss the risks and benefits of this medication with your doctor.

The following side effects have been reported by at least 1% of people taking this medication. Many of these side effects can be managed, and some may go away on their own over time.

Contact your doctor if you experience these side effects and they are severe or bothersome. Your pharmacist may be able to advise you on managing side effects.

• abdominal pain
• cold or flu-like symptoms (e.g., runny or stuffy nose, sore throat, headache)
• constipation
• cough
• decreased appetite
• decreased interest in sexual activity
• decreased sexual ability
• diarrhea
• dizziness
• drowsiness
• fatigue
• headache
• indigestion
• nausea
• sensitivity to the sun
• skin rash
• upset stomach
• vomiting
• weakness (loss of strength)

Although most of the side effects listed below don’t happen very often, they could lead to serious problems if you do not seek medical attention.

Check with your doctor as soon as possible if any of the following side effects occur:

• discoloured patches or lumps on the skin that change slowly over time
• dizziness when rising from a sitting or lying position, lightheadedness, or fainting (signs of low blood pressure)
• joint pain (e.g., toe pain may be a sign of gout)
• muscle cramps
• signs of anemia (low red blood cells; e.g., dizziness, pale skin, unusual tiredness or weakness, shortness of breath)
• signs of bleeding (e.g., unusual nosebleeds, bruising, blood in urine, coughing blood, bleeding gums, cuts that don’t stop bleeding)
• signs of infection (symptoms may include fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness)
• signs of kidney problems (e.g., decreased urination, nausea, vomiting, swelling of legs or hands, fatigue)
• signs of liver problems such as abdominal pain, nausea or vomiting, itching of skin, yellow eyes or skin
• signs of pancreatitis (e. g., abdominal pain on the upper left side, back pain, nausea, fever, chills, rapid heartbeat, swollen abdomen)
• signs of too much or too little potassium in the body
• dry mouth
• increased thirst
• irregular heartbeat
• mood or mental changes
• muscle cramps or pain
• numbness or tingling in hands, feet, or lips
• weak pulse
• weakness or heaviness of legs
• symptoms of lupus (e.g., skin rash (with or without itching), fever, or joint pain)
• swelling of hands, ankles or feet
• symptoms of high blood sugar (e.g., frequent urination, increased thirst, excessive eating, unexplained weight loss, poor wound healing, infections, fruity breath odour)
• symptoms of fast heartbeat (e.g., dizziness, lightheadedness, shortness of breath, racing heartbeat)

Stop taking the medication and seek immediate medical attention if any of the following occur:

• chest pain
• severe skin rash, including skin blistering and peeling (possibly with headache, fever, coughing, or aching before the rash begins)
• symptoms of a serious allergic reaction, including angioedema (e. g., hives; swelling of the face, mouth, hands, or feet; and difficulty breathing)
• symptoms of increased pressure in the eyes or other eye problems (e.g., blind spots, decreased or blurred vision, eye pain, sudden near sightedness, red eye, swelling of the eye)

Some people may experience side effects other than those listed. Check with your doctor if you notice any symptom that worries you while you are taking this medication.

Are there any other precautions or warnings for this medication?

Before you begin taking a medication, be sure to inform your doctor of any medical conditions or allergies you may have, any medications you are taking, whether you are pregnant or breast-feeding, and any other significant facts about your health. These factors may affect how you should take this medication.

Allergic reaction: Some people who are allergic to sulfonamide medications also experience allergic reactions to hydrochlorothiazide. Before you take this medication, inform your doctor about any previous adverse reactions you have had to medications, especially to sulfonamide antibiotics or diabetes medications. Contact your doctor at once if you experience signs of an allergic reaction, such as skin rash, itching, difficulty breathing, or swelling of the face and throat.

Allergy desensitization treatment: Tell your doctor if you are undergoing or will undergo desensitization treatment for an allergy. Desensitization treatment reduces the effects of the allergy (e.g., the reaction to bee or wasp stings), but it can sometimes cause a more severe allergic reaction if you are taking ACE inhibitors during the desensitization treatment.

Angioedema: Angioedema is a serious allergic reaction that causes swelling of the hands, feet, ankles, face, lips, tongue, or throat. If you experience any of these when you take lisinopril – hydrochlorothiazide, stop taking the medication at once and get immediate medical attention.

You should avoid taking any other medications in the ACE inhibitors class of medications. People who have had angioedema caused by other substances may be at increased risk of angioedema when they take an ACE inhibitor.

Cholesterol: Increases in cholesterol and triglyceride levels may occur when taking hydrochlorothiazide. At the doses used in lisinopril – hydrochlorothiazide, this rarely causes problems. However, if you have high cholesterol, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Cough: People taking lisinopril may develop a dry, persistent cough that usually disappears only after stopping or lowering the lisinopril dose of this medication. Inform your doctor of any cough that does not seem to be related to a usual cause.

Diabetes: Hydrochlorothiazide may make it more difficult for people who have diabetes to control their blood sugar. High blood sugar may occur, glucose tolerance may change, and diabetes may worsen. A dose adjustment of diabetes medications, including insulin, may be required. If you have diabetes, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.  An adjustment to doses of antidiabetic medications may be required.

Drowsiness/reduced alertness: Lisinopril – hydrochlorothiazide can cause dizziness or tiredness and you should not perform tasks such as driving or using machines that require special attention until you know how the medication will affect you.

Fluid and electrolyte balance: Increases in blood levels of potassium may occur for some people who take lisinopril. The levels of electrolytes such as calcium, potassium, sodium, magnesium, and chloride can be affected by treatment with hydrochlorothiazide. Your doctor will periodically check to see if these are in balance by requesting blood tests. Warning signs of fluid and electrolyte imbalance include:

• confusion
• drowsiness
• dryness of mouth
• lethargy
• low blood pressure
• muscle pains or cramps
• muscular fatigue
• nausea
• racing heartbeat
• restlessness
• seizures
• thirst
• vomiting
• weakness

Glaucoma: This medication may cause the symptoms of glaucoma (increased pressure in the eye) to become worse. Report any changes in vision to your doctor as soon as possible while you are taking this medication.

Gout: Hydrochlorothiazide may increase the level of uric acid in the body, which may result in an attack of gout. If you have a history of gout, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you develop painful, warm, and swollen joints, contact your doctor.

Heart or blood vessel disease: If you have a narrowing of the aorta (aortic stenosis) or the kidney artery (renal artery stenosis), or increased thickness of the heart muscle (hypertrophic cardiomyopathy), discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Kidney function: Decreased kidney function or kidney disease can cause this medication to build up in the body, causing side effects. Lisinopril may cause decreased kidney function. Certain people, such as those with narrowed blood vessels in their kidneys, or those with severe congestive heart failure may be more likely to experience this complication. The use of other diuretics (water pills), nonsteroidal anti-inflammatory drugs (NSAIDs), or aliskiren, may further increase risk of kidney trouble for people already at risk for this problem. If you have reduced kidney function, renal artery stenosis (narrowing of blood vessels in the kidneys), or congestive heart failure, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. If you have reduced kidney function, you may require lower doses of this medication.

If you experience symptoms of decreased kidney function, such as puffy hands, face, or feet; high blood pressure; unusual muscle cramping; or darkened urine, this medication may be affecting how well your kidneys are working. If you notice any of these symptoms, contact your doctor as soon as possible.

Liver function: Liver disease or reduced liver function may cause this medication to build up in the body, causing side effects. This medication can also worsen liver function. If you have liver problems, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed. Your doctor may want to test your liver function regularly with blood tests while you are taking this medication. If you notice any signs of liver problems (e.g., abdominal pain, itching of skin, or yellow eyes or skin, loss of appetite, vomiting), contact your doctor immediately.

Low blood pressure: Occasionally, blood pressure drops too low after taking lisinopril – hydrochlorothiazide. This usually happens after the first or second dose or when the dose is increased. It is more likely to occur for people who take water pills, have a salt-restricted diet, are on dialysis, are taking the medication aliskiren, are suffering from diarrhea or vomiting, or have been sweating excessively and not drinking enough liquids. If low blood pressure causes you to faint or feel lightheaded, contact your doctor.

Low white blood cell count: This medication can decrease the number of white blood cells, which help the body to fight infection. Your doctor may periodically request blood tests to monitor your levels of white blood cells. If you notice more frequent signs of infection (e.g., fever, chills, or sore throat), contact your doctor immediately.

Lupus: There have been reports of a worsening or activation of lupus for people taking hydrochlorothiazide. If you have lupus, discuss with your doctor how this medication may affect your medical condition, how your medical condition may affect the dosing and effectiveness of this medication, and whether any special monitoring is needed.

Sensitivity to sunlight: This medication may increase the sensitivity of the skin to sunlight, increasing the risk of sunburn. Avoid exposure to sunlight for long periods of time, particularly between the hours of 10 am and 2 pm, while you are taking this medication. Wear a broad-spectrum sunscreen and lip balm with an SPF of 30 or greater. If you notice any unusual skin rash or peeling, contact your doctor immediately.

Skin cancer: Recent reviews of hydrochlorothiazide have connected long term use of the medication with an increased risk of developing non-melanoma skin cancer. This often appears as a lump or discoloured patch of skin that slowly changes appearance or size. Check your skin regularly for unusual growths or discolouration and report any changes to your doctor as soon as possible. Talk to your doctor about any concerns you may have.

Surgery or anesthesia: Tell your doctor or dentist that you are taking lisinopril – hydrochlorothiazide before you are given a local or general anaesthetic. When combined with some anesthetics, this medication may cause a short-term drop in blood pressure.

Pregnancy: Pregnant women should not take this medication. When used during pregnancy, lisinopril can cause injury or death to the developing baby. If you become pregnant, stop taking this medication and contact your doctor immediately.

Breast-feeding: Medications similar to lisinopril pass into breast milk and hydrochlorothiazide passes into breast milk. If you are breast-feeding and are taking lisinopril – hydrochlorothiazide, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding.

Children: The safety and effectiveness of this medication have not been established for children. It is not recommended for children to use this medication.

Seniors: Seniors have an increased risk of experiencing side effects when taking quinapril lisinopril – hydrochlorothiazide due to reduced kidney function. Lower doses may be necessary to minimize side effects.

What other drugs could interact with this medication?

There may be an interaction between lisinopril – hydrochlorothiazide and any of the following:

• acetylsalicylic acid (ASA)
• aclidinium
• alcohol
• aldesleukin
• aliskiren
• allopurinol
• alpha-adrenergic blocking agents (e.g., alfuzosin, doxazosin, prazosin, terazosin)
• alpha-agonists (e.g., clonidine, methyldopa)
• angiotensin converting enzyme inhibitors (ACEIs; captopril, enalapril, ramipril)
• amiodarone
• amphetamines (e. g., dextroamphetamine, lisdexamfetamine)
• angiotensin receptor blockers (ARBs; losartan, valsartan, candesartan)
• antacids (e.g., aluminum hydroxide, calcium carbonate, magnesium hydroxide)
• antihistamines (e.g., azelastine, cetirizine, doxylamine, diphenhydramine, hydroxyzine, loratadine)
• antipsychotics (e.g., chlorpromazine, clozapine, haloperidol, olanzapine, quetiapine, risperidone)
• apomorphine
• atropine
• azathioprine
• azelastine
• barbiturates (e.g., butalbital, phenobarbital)
• belladonna
• benztropine
• beta-blockers (e.g., atenolol, carvedilol, propranolol)
• beta-2 agonists (e.g., salbutamol, formoterol, terbutaline)
• brimonidine
• calcitriol
• calcium carbonate, calcium citrate
• calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
• carbamazepine
• cholestyramine
• colestipol
• conivaptan
• oral corticosteroids (e. g., dexamethasone, hydrocortisone, prednisone)
• cyclobenzaprine
• cyclophosphamide
• cyclosporine
• desmopressin
• dexmethylphenidate
• diabetes medications (e.g., acarbose, canagliflozin, glyburide, lixisenatide, insulin, metformin, rosiglitazone, saxagliptin)
• diazoxide
• digoxin
• disopyramide
• domperidone
• drospirenone
• duloxetine
• eplerenone
• everolimus
• flavoxate
• ginger
• ginseng
• glycopyrrolate
• grass pollen extract
• guanfacine
• heparin
• hydralazine
• inhaled corticosteroids (e.g., budesonide, ciclesonide, fluticasone)
• ipratropium
• iron dextran complex
• iron supplements
• ivabradine
• lanthanum
• levodopa
• licorice
• lithium
• low molecular weight heparins (LMWHs; e.g., dalteparin, enoxaparin, tinzaparin)
• medications that increase blood levels of potassium (e. g., potassium chloride, salt substitutes containing potassium)
• methylphenidate
• monoamine oxidase inhibitors (MAOIs; e.g., moclobemide, phenelzine, rasagiline, selegiline, tranylcypromine)
• multivitamins/minerals with ADE
• nabilone
• narcotic pain relievers (e.g., codeine, fentanyl, morphine, tramadol)
• nitroglycerin
• nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen)
• obinutuzumab
• octreotide
• orphenadrine
• other diuretics (water pills; e.g., furosemide, triamterene)
• oxcarbazepine
• oxybutynin
• pentoxifylline
• phenytoin
• phosphodiesterase-5 inhibitors (e.g., sildenafil, tadalafil, vardenafil)
• porfimer
• pramipexole
• pregabalin
• riociguat
• ropinirole
• sacubitril
• scopolamine
• selective serotonin reuptake inhibitors (SSRIs; e.g., citalopram, fluoxetine, paroxetine, sertraline)
• sirolimus
• sodium phosphates
• temsirolimus
• tiotropium
• tizanidine
• tolterodine
• tolvaptan
• topiramate
• tretinoin
• tricyclic antidepressants (e. g., amitriptyline, clomipramine, desipramine, trimipramine)
• trimethoprim
• umeclidinium
• vitamin D
• yohimbine

If you are taking any of these medications, speak with your doctor or pharmacist. Depending on your specific circumstances, your doctor may want you to:

• stop taking one of the medications,
• change one of the medications to another,
• change how you are taking one or both of the medications, or
• leave everything as is.

An interaction between two medications does not always mean that you must stop taking one of them. Speak to your doctor about how any drug interactions are being managed or should be managed.

Medications other than those listed above may interact with this medication. Tell your doctor or prescriber about all prescription, over-the-counter (non-prescription), and herbal medications you are taking. Also tell them about any supplements you take. Since caffeine, alcohol, the nicotine from cigarettes, or street drugs can affect the action of many medications, you should let your prescriber know if you use them.

All material copyright MediResource Inc. 1996 – 2023. Terms and conditions of use. The contents herein are for informational purposes only. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Source: www.medbroadcast.com/drug/getdrug/Mylan-Lisinopril-HCTZ

The choice of a fixed combination of lisinopril and hydrochlorothiazide in the treatment of arterial hypertension | Savenkov M.P., Ivanov S.N., Solomonova L.A., Savenkova A.M., Ivanov S.V.

Currently, due to the active introduction into the practice of treating arterial hypertension (AH) of a wide range of drug combinations fixed in one tablet, the practitioner is increasingly faced with the problem of their choice. In accordance with modern recommendations, the reasons for the combined use of drugs are the presence of different and complementary mechanisms of action, evidence of greater effectiveness of the combination, as well as good tolerability of treatment and a lower risk of side effects [1]. The most common fixed combination for the treatment of hypertension is the combination of an ACE inhibitor with a thiazide diuretic [2]. However, the combination of an ACE inhibitor with a calcium channel blocker (CCB), a CCB with a b-blocker (BAB), a BAB with a diuretic, and others are beginning to compete with this combination. The evidence base is accumulating, indicating the effectiveness of the listed antihypertensive combinations, which makes it difficult to differentiate them based on traditional criteria that take into account the age of patients, their race, the presence of target organ damage and associated clinical conditions. Along with the choice of drugs, their correct dosing plays an important role. The latter presents certain difficulties associated with the need to titrate the therapeutic effect with a subordinate change in the dosages of the combination components. The available clinical experience with the use of fixed drugs indicates that the treatment of patients with hypertension should be carried out according to certain indications and with the help of control methods that take into account the mechanisms and specifics of the action of the drug combination.

The use of a fixed combination of an ACE inhibitor and a diuretic suggests that the patient has hypertension with fluid and electrolyte disturbances. In accordance with the modern concept of cardiorenal relationships, renal mechanisms are age dependent and are observed in all patients with AH at a certain stage of the disease [3]. For this reason, ACE inhibitors, which have a triple (vasodilating, diuretic and sympatholytic) effect due to a decrease in the formation of angiotensin II, are most widely used in practice to reduce elevated blood pressure. Limitations in the use of these drugs are associated with the possible development of cough (1-3%), pregnancy and renal artery stenosis. The leading position among the numerous representatives of ACE inhibitors is lisinopril, an active hydrophilic drug with a long (more than 24 hours) action that does not require primary metabolic activation in the liver and does not accumulate in adipose tissue [3,4,5]. These properties provided the benefits of the drug in the morning hours, in obese patients, when combined with other drugs, as well as in various comorbid conditions [6-8]. Conducted multicenter studies have confirmed the ability of lisinopril to improve the prognosis of patients with cardiovascular disease and their quality of life [5]. Lisinopril is taken once a day, and with fluctuations in daily dosage from 5 to 20 mg, effective control of blood pressure can be achieved in 60% of cases or more.
In the Russian Federation, the first representative of lisinopril was Diroton® by Gedeon Richter, Hungary. Our many years of experience in the use of lisinopril (Diroton) indicates that monotherapy can effectively control blood pressure, mainly at the initial stages of the formation of hypertension, in patients with low and moderate risk of developing cardiovascular complications (CVD), as well as in relatively stable meteorological conditions. The antihypertensive effect of lisinopril is reduced in patients with a long history of hypertension and a high risk of cardiovascular events, especially in active smokers with signs of nephropathy. The effectiveness of the drug also decreases during weather-unstable (winter-spring) seasonal periods against the background of sharp fluctuations in atmospheric pressure, humidity and air temperature [9]. Due to the risk of increased side effects, increasing the daily dose of lisinopril by more than 20 mg is not advisable. In case of insufficient effectiveness of treatment, it is necessary to transfer the patient to the combined use of lisinopril with an antihypertensive drug of a different mechanism of action, in particular, a thiazide diuretic or CCB amlodipine.
The use of a thiazide diuretic in combination with lisinopril leads to an increase in the antihypertensive effect and a decrease in the risk of adverse reactions. It is believed that the decrease in elevated blood pressure when using a diuretic occurs as a result of the removal of water and sodium chloride, which leads to a decrease in circulating blood volume and cardiac output, as well as a decrease in vascular tone, total peripheral resistance as a result of a decrease in the response of the vascular wall to catecholamines and angiotensin II .
More than half a century of experience in clinical use has made it possible to formulate two basic rules for the use of diuretics: these drugs should be prescribed only in the presence of water and electrolyte disorders and in the minimum effective doses. The last provision is extremely important, because. can significantly reduce the risk of side effects with long-term (actually lifelong) use of diuretics in the treatment of hypertension. A large number of multicenter studies have shown that long-term use of thiazide (hydrochlorothiazide) and thiazide-like (indapamide) diuretics in low doses, respectively, in the ranges of 6.25-25 mg and 0.625-2.5 mg is safe [10]. At the same time, it should be noted that, in fact, a four-fold range of diuretic dosage fluctuations is quite wide, and therefore the problem of choosing the minimum effective antihypertensive dose remains relevant, especially considering that the diabetogenic effect with very long-term use of tazide diuretics is not completely excluded, as there is a corresponding warning in the recommendations of the European Society of Cardiology [1]. Diuretics remain the treatment of choice in the treatment of isolated systolic hypertension in elderly patients; they are widely used in practice to enhance the antihypertensive effect of other drugs, primarily ACE inhibitors. The feasibility and necessity of using a combination of an ACE inhibitor with a thiazide diuretic for more effective control of blood pressure and the prevention of vascular complications (in particular, stroke) has been convincingly proven by multicenter studies [11].
For more convenient administration and increased adherence of patients to treatment, ACE inhibitors and diuretics are increasingly being used in one tablet in fixed therapeutic doses. Currently, a large group of such combined drugs has been replenished with another representative – a combination of an ACE inhibitor lisinopril with hydrochlorothiazide. The effectiveness of this combination was confirmed at the end of the last century, when during the examination and treatment of more than 800 patients with hypertension, it was shown that when hydrochlorothiazide, inferior in its antihypertensive activity, is added to lisinopril, a significantly greater decrease in elevated blood pressure occurs, while the risk of developing hypokalemia decreases. It was also found that the use of lisinopril at a dose of 10 mg with hydrochlorothiazide 12.5 mg is optimal. This combination is especially effective in elderly patients [12-14].
In the Russian Federation, a fixed combination of lisinopril with hydrochlorothiazide in doses of 10/12.5 and 20/12.5 mg is registered under the trade name Co-Diroton® (Gedeon Richter, Hungary). The accumulating, including our own, experience with the use of Co-Diroton indicates the prospects of its use for the treatment of hypertension. Taking into account the complex cardiorenal mechanism of action of Co-Diroton, its effectiveness was studied using the method of combined 24-hour monitoring of blood pressure and diuresis (CSMAD) developed by us [15].
KSMADD includes simultaneous monitoring of blood pressure according to the generally accepted method and diuresis in the form of a percentage of the volume of urine excreted and fluid consumed for the morning, noon, evening and night periods of time [15]. The main indicator of KSMADD is the tensiodiuretic ratio (TDS) – a complex indicator that reflects the average value of systolic blood pressure for a given period of time (t), and diuresis as a percentage of the ratio of excreted urine to fluid consumed over the same period (TDSt = sred.AP syst. mm Hg / diuresis %). In healthy individuals, normal TDS values ​​range from 120–135 mm Hg / 75–100%. TDS allows you to determine the relationship between blood pressure and diuresis at different times of the day.
The experience of using KSMAD in more than 200 patients with cardiovascular pathology suggests that the magnitude of TDS can be used to evaluate the effectiveness of treatment for hypertension, including a thiazide diuretic in the dynamics of diuresis (Fig. 1). The study during the QSMAD diuresis revealed the presence of daytime fluid retention in patients with AH, followed by its more intense release at night (Fig. 1). Activation of nocturnal diuresis in patients occurred against the background of elevated blood pressure.
The revealed relationships between diuresis and blood pressure make it possible to understand the reason for the absence of a nocturnal decrease in blood pressure in hypertensive patients and to evaluate daytime fluid retention as a manifestation of water imbalance, justifying the need to prescribe a thiazide diuretic for antihypertensive purposes. The appointment of the latter leads to a decrease in blood pressure due to the activation of daytime diuresis and a decrease in night diuresis (Fig. 1). The use of KSMADD allows you to justify the choice and evaluate the effectiveness of the fixed combination of lisinopril with hydrochlorothiazide.
This combination (Ko-Diroton®, Gedeon Richter, Hungary) was used in 15 patients (11 men and 4 women) aged 56–75 years with hypertension of II–III degree, with a high gradation of risk, in whom preliminary treatment was carried out for 3–4 weeks of monotherapy with lisinopril (Diroton®, Gedeon Richter, Hungary) at a daily dose of 10–20 mg, was not effective enough, according to the KSMADD. Of the 15 patients, 9 were long-term smokers, 8 patients were overweight. All patients led a sedentary lifestyle. 5 patients had stable exertional angina I-II functional class. The study was conducted in the autumn-winter period against the background of unstable weather conditions in the form of periodic fluctuations in atmospheric pressure at a rate of > 0.5 mm.h, changes in outdoor air temperature (from +15 to -20°C) and air humidity from 55 to 98%. Existing risk factors in patients and changes in weather conditions were possible reasons for the insufficient effectiveness of lisinopril monotherapy. Co-Diroton was prescribed in fixed doses: lisinopril – 10 mg, hydrochlorothiazide – 12.5 mg. The effectiveness of treatment was assessed at 3-4 weeks of treatment. In the absence of a targeted reduction in blood pressure, the dose of lisinopril was doubled, i.e., Co-Diroton was prescribed in the ratio of dosages of lisinopril and hydrochlorothiazide – 20/12.5 mg. The effectiveness of treatment was assessed using QSMADD according to the dynamics of TDS.
Figure 2 shows the dynamics of TDS indicators during monotherapy with lisinopril and the use of a fixed combination of lisinopril with hydrochlorothiazide. As a result of monotherapy with lisinopril, there was a slight decrease in blood pressure, but it was insufficient and was accompanied by a decrease in diuresis in the morning and evening.
Against the background of the use of a fixed combination of lisinopril with hydrochlorothiazide, there was an additional decrease in blood pressure, an increase in daytime diuresis and a decrease in nighttime diuresis (Fig. 2). The revealed dynamics of blood pressure and diuresis makes it possible to explain the achieved antihypertensive effect by restoring the circadian water and electrolyte balance. The target reduction in blood pressure was achieved in 12 out of 15 patients, and in 3 cases it was required to use Co-Diroton with a fixed dose of lisinopril 20 mg, in 3 cases – a calcium channel blocker – amlodipine at a dose of 2.5 mg. The treatment was well tolerated by patients, and only in one case was a transient appearance of coughing, which passed on its own without discontinuation of the drug. Our study allowed us to give a positive assessment of the therapeutic efficacy of the fixed combination of lisinopril with hydrochlorothiazide (Co-Diroton), to determine the list of clinical situations in which the use of this drug will have certain advantages. The latter include:
• advanced age of patients;
• smoking, physical inactivity, overweight and other risk factors that contribute to fluid retention in the body;
• insufficient effect of monotherapy with an ACE inhibitor;
• increase in blood pressure against the background of a decrease in daily diuresis;
• lack of nightly decrease in blood pressure;
• the presence of microalbuminuria and other signs of nephropathy;
• the presence of heart failure;
• meteorological instability with sharp fluctuations in atmospheric pressure.
The use of the fixed combination of lisinopril with hydrochlorothiazide should be limited during periods of extremely hot weather and in other cases, accompanied by a significant loss of fluid and electrolytes. In these situations, the significance of diuresis testing is greatly reduced, and measurement of the patient’s weight should be used to assess fluid balance.
The antihypertensive effect of the fixed combination of lisinopril with hydrochlorothiazide can be enhanced by the additional administration of the calcium channel blocker amlodipine.

Literature
1. 2007 recommendations for the treatment of arterial hypertension. Rational Pharmacotherapy in Cardiology 2008;(1–2):2–76
2. Mukhin N.A., Moiseev B.C., Kobalava Zh.D. Cardiorenal interactions: clinical significance and role in the pathogenesis of diseases of the cardiovascular system and kidneys. Ter archive 2004; 6:39–46
3. Opie LH. Angiotensin–converting enzyme inhibitors: scientific basis for clinical use. John Wiley & Sons: New York, 1992.
4. Jaiani N.A. Cardioprotective and nephroprotective effects of angiotensin-converting enzyme inhibitors. Russian medical journal. 2005; 27: 1858–1863
5. Kutishenko N.P., Martsevich S.Yu. Angiotensin-converting enzyme inhibitor lisinopril: features of use in cardiology. Atmosphere 2007;(2):2–5.
6. Savenkov M.P., Ivanov S.N., Botsoeva M.A., Mikhailusova M.P. Correction of high blood pressure in the morning with ACE inhibitors. Gedeon Richter in the CIS 2001;4(8):27–30.
7. Kislyak O.A. ACE inhibitor lisinopril in the treatment of elderly patients with isolated systolic and systolic-diastolic arterial hypertension. Medical business 2007;(2):2–7.
8. Oshchepkova E.V. Possibilities of the angiotensin-converting enzyme inhibitor lisinopril (Diroton) in the treatment of patients with arterial hypertension with concomitant liver pathology. Atmosfera.Kardiology 2007;(3):1–4.
9. Savenkov M.P., Kirichenko A.V., Ivanov S.N. , et al. Seasonal adjustment of antihypertensive therapy. Consilium Medicum.2008, v.10, no.5 p.17–20
10. Kobalava, Zh. D. Treatment of arterial hypertension: diuretics. Russian medical journal. 2000; Volume 8, No. 4, p. 15–18.
11. Kobalava Zh.D., Villevalde S.V. Diuretics are the cornerstone of modern antihypertensive therapy. Consilim medicum. v. 11 Vol. No. 4, p. 24–27
12. Pool J.L., Gennari J., Goldstein R. e.a. Controlled multicenter study of the antihypertensive effects of lisinopril, hydrochlorthiazide and lisinopril plus hydrochlorthiazide in the treatment of 349patients with mild to moderate tssential hypertension. J. Cardiovasc. Pharmacol. 1987 9(suppl.3) S 36–54
13. Leduc J.J., Madonna O., Grossin V. Evaluation of lisinopril–hydrochlorthizide combination in mild to moderate hypertension. Therapie 1994 49(1) 17–22
14. Mancia G., Grassi G. Antihypertensive effects of combined lisinopril and hydrochlortiazide in elderly patients with systolic hypertension: results of a multicenter trial. J. Cardivasc. Pharmacol. 1997, 30(5) 548–553
15. Savenkov M.P., Kirichenko A.V., Borshchevskaya M.V., Ivanov S.N. Individual selection of diuretic therapy using combined monitoring of diuresis and blood pressure in patients with arterial hypertension and heart failure. Russian journal of cardiology. 2009; No. 6, pp. 19–24.

Lisinopril-N 10 mg / 12.5 mg tablets No. 30

Composition:

active ingredients: 1 tablet contains lisinopril dihydrate in terms of 100% substance 10 mg or 20 mg and hydrochlorothiazide 12.5 mg

excipients: mannitol (E 421), magnesium stearate, calcium hydrogen phosphate, corn starch, pregelatinized corn starch.

Dosage form

Tablets.

Basic physical and chemical properties:

white or off-white flat-cylindrical tablets with beveled edges and notch on one side.

Pharmacological group

ACE inhibitors (ACE inhibitors) and diuretics.

ATX code C09B A03.

Pharmacological properties

Pharmacological properties.

Lisinopril-N is a fixed dose combination of lisinopril, an ACE inhibitor (ACE), and hydrochlorothiazide, a thiazide diuretic. Both components show a complementary and additive antihypertensive effect.

Lisinopril is a peptidyl dipeptidase inhibitor. It inhibits ACE, which catalyzes the conversion of angiotensin I to the vasoconstrictor peptide, angiotensin II. Angiotensin II also stimulates the secretion of aldosterone in the adrenal cortex. Suppression of ACE leads to a decrease in the concentration of angiotensin II, which leads to a decrease in vasopressor activity and a decrease in aldosterone secretion. Further reduction may lead to an increase in serum potassium.

Although the mechanism by which lisinopril lowers blood pressure is thought to be primary renin-angiotensin-inhibition, lisinopril lowers blood pressure even in patients with low-renin hypertension. ACE is identical to kininase II, an enzyme that breaks down bradykinin. It is not known whether elevated levels of bradykinin, a potent vasodilator peptide, play a role in the therapeutic effects of lisinopril.

Hydrochlorothiazide is a diuretic and antihypertensive agent. It affects the mechanism of electrolyte reabsorption in the distal tubular kidney and increases the excretion of sodium and chloride in approximately the same way. Natriuresis may be accompanied by some loss of potassium and bicarbonate. The mechanism of the antihypertensive action of thiazides is unknown. Thiazides usually do not affect normal blood pressure.

Non-melanoma skin cancer.

The results of two pharmacoepidemiological studies based on data from the Danish National Cancer Registry demonstrated a cumulative dose-dependent relationship between hydrochlorothiazide (HCTZ) and the occurrence of basal cell carcinoma (BCC) and plascoclitin carcinoma (PCC).

One study included a population of 71533 patients with CCC and 8629 patients with RCC compared with 1430833 and 172462 patients from the control population, respectively. The use of high doses of HCTZ (≥50,000 mg cumulatively) was associated with an adjusted hazard ratio (HR) of 1.29 (95% confidence interval (CI): 1.23-1.35) for CCC and 3.98 (95% CI : 3.68-4.31) for PCC. A clear cumulative dose-dependent relationship was observed for both CCB and RCC.

Another study showed a possible association between lip cancer (LCC) and HCTZ use: 633 cases of lip cancer (LCC) were compared with 63067 patients in a control population using a random sampling strategy. A cumulative dose-response relationship was demonstrated with an adjusted CR of 2.1 (95% CI: 1.7-2.6), which increased to CR3.9 (3.0-4.9) for high doses (~25,000 mg) and CR 7.7 (5.7-10.5) for a high cumulative dose (~ 100,000 mg) (see section “Peculiarities of use”).

Pharmacokinetics.

Co-administration of lisinopril and hydrochlorothiazide has little or no effect on the bioavailability of both components. There were no clinically significant pharmacokinetic interactions between the two components when taken in 1 tablet.

Lisinopril.

Absorption. After taking lisinopril, the maximum plasma concentration is reached within about 7:00. Based on urinary excretion data, the mean absorption of lisinopril over the dose range studied (5-80 mg) is approximately 25% with an interindividual variation of 6-60%. Bioavailability is reduced by approximately 16% in patients with heart failure. Absorption of lisinopril does not depend on food intake.

Distribution. Probably, lisinopril does not bind to plasma proteins, except for circulating ACE.

Lisinopril is known to poorly cross the blood-brain barrier.

Removal. Lisinopril is not metabolized and is excreted by the kidneys completely unchanged. With repeated administration, lisinopril has an effective accumulation half-life of 12.6 hours. The clearance of lisinopril in healthy volunteers is approximately 50 ml/min. A decrease in serum concentration indicates a prolonged terminal phase, which is not a consequence of cumulation of the drug. This terminal phase may indicate saturation of ACE binding and is not dose proportional.

Heart failure. Patients with heart failure are more exposed to lisinopril compared to healthy volunteers (an increase in the area under the concentration-time curve (AUC) by an average of 125%). Based on the data on the withdrawal of lisinopril in the urine, it turned out that there is a decrease of approximately 16% absorption compared with healthy volunteers.

Elderly patients. Elderly patients have higher plasma AUC values ​​(increased by about 60%) compared to younger volunteers.

Impaired kidney function. Impaired renal function reduces the elimination of lisinopril, which is excreted by the kidneys, but this decrease becomes clinically significant only when the glomerular filtration rate is below 30 ml / min. In mild to moderate renal failure (creatinine clearance ≥ 30-<80 ml / min), the average AUC was increased by only 13%, while in severe renal failure (creatinine clearance ≥ 5-<30 ml / min) - 4. 5 times.

Lisinopril can be eliminated from the body by dialysis. During 4 hours of hemodialysis, plasma concentrations of lisinopril decreased by an average of 60%, clearance on dialysis was in the range of 40 to 55 ml/min.

Impaired liver function. Impaired liver function in patients with cirrhosis led to a decrease in the absorption of lisinopril (about 30% when determined by urinary excretion), but an enhanced effect (about 50%) compared with healthy volunteers, due to a decrease in clearance.

Hydrochlorothiazide.

Hydrochlorothiazide is rapidly absorbed from the digestive tract. In humans, approximately 70% of an orally administered therapeutic dose is absorbed primarily in the duodenum and upper small intestine. Eating does not affect absorption, and the maximum concentration is reached within 2-4 hours after ingestion. The volume of distribution has been reported to be between 0.8 and 3 L/kg. Hydrochlorothiazide is not metabolized but is rapidly excreted by the kidneys. At least 61% of the dose is excreted unchanged within 24 hours. The half-life is from 8 to 12:00, and 95% of absorbed hydrochlorothiazide is excreted by the kidneys. After taking hydrochlorothiazide, diuresis begins after 2:00, the peak occurs at about 4:00 and lasts 6-12 hours. Hydrochlorothiazide crosses the placenta but does not cross the blood-brain barrier.

indications

Arterial hypertension of mild or moderate severity, has a stable course during therapy with lisinopril and hydrochlorothiazide in the same dosages.

Contraindications

– hypersensitivity to lisinopril and other ACE inhibitors, to hydrochlorothiazide and sulfonamide derivatives or other components of the drug.

– history of angioedema associated with the use of ACE inhibitors.

– hereditary or idiopathic angioedema.

– Hemodynamically significant aortic or mitral valve stenosis or hypertrophic cardiomyopathy.

– Severe renal insufficiency or end-stage disease.

– Severe liver disease.

– exacerbation of gout.

– Anuria.

– Hyperuricemia.

– Hyperaldosteronism.

– renal artery stenosis (bilateral or unilateral).

– cardiogenic shock.

– Hemodynamically unstable condition after acute myocardial infarction.

– performing hemodialysis using high-flow membranes (eg AN 69).

– Serum creatinine > 220 µmol/l.

– Simultaneous use of aliskiren-containing drugs in patients with diabetes mellitus or impaired renal function (GFR <60 ml / min / 1.73 m2).

– Pregnancy planning.

– the period of pregnancy and lactation.

– children’s age (up to 18 years).

Interaction with other medicinal products and other forms of interaction

Diuretics. The use of a diuretic at the peak of lisinopril therapy will provide an additional antihypertensive effect.

Symptomatic hypotension may develop after the first dose of Lisinopril-N. The development of this condition is more likely in patients with dehydration and / or lack of salt as a result of previous diuretic therapy. The use of diuretics should be discontinued prior to initiation of Lisinopril-N therapy.

Dietary supplements containing potassium, potassium-sparing diuretics or salt substitutes containing potassium. Potassium excretion while taking thiazide diuretics is usually attenuated by the potassium-sparing effect of lisinopril. The use of dietary supplements containing potassium, potassium-sparing substances or salt substitutes containing potassium, especially in patients with impaired renal function, can lead to a significant increase in serum potassium. If the simultaneous use of the drug and any of these substances is necessary, they should be used with caution against the background of frequent monitoring of the content of potassium in the blood serum.

Tricyclic antidepressants/antipsychotics/anesthetics. The simultaneous use of anesthetics, tricyclic antidepressants or antipsychotics and ACE inhibitors may lead to an additional decrease in blood pressure.

Narcotic / antipsychotic drugs. Against the background of taking ACE inhibitors, orthostatic hypotension may develop.

Barbiturates or narcotics. May increase orthostatic hypotension.

Non-steroidal anti-inflammatory drugs (NSAIDs) / anti-inflammatory drugs. Long-term use of NSAIDs (selective COX-2 inhibitors, acetylsalicylic acid more than 3 g / day and non-selective NSAIDs) can reduce the hypotensive effect of both the ACE inhibitor and the thiazide. Concomitant use of NSAIDs and ACE inhibitors may impair renal function. This effect is usually transient. In rare cases, acute renal failure may develop, primarily in patients with impaired renal function, it occurs in the elderly, and in patients in a state of dehydration.

In some patients, NSAIDs may decrease the diuretic, natriuretic, and antihypertensive effects of diuretics.

Elevated serum potassium levels have been reported with NSAIDs and ACE inhibitors, which may lead to impaired renal function.

Sympathomimetics. Sympathomimetics can reduce the hypotensive effect of ACE inhibitors.

Other antihypertensive drugs. The antihypertensive effect of Lisinopril-N can be enhanced with the simultaneous administration of other drugs, which can probably lead to orthostatic hypotension. The simultaneous use of glyceryl trinitrate and other nitrates or other vasodilators may further reduce blood pressure.

Acetylsalicylic acid, thrombolytics, β-blockers, nitrates. Lisinopril-N can be used simultaneously with acetylsalicylic acid (in cardiac doses), thrombolytics, β-blockers and / or nitrates.

Antidiabetic drugs. It is known that the simultaneous use of ACE inhibitors and antidiabetic drugs (insulin, oral hypoglycemic drugs) can lead to increased hypoglycemic effect with the risk of hypoglycemia. The possibility of this phenomenon is more likely during the first 2 weeks of combination therapy and in patients with impaired renal function.

Glucose tolerance may be impaired, so it may be necessary to change the dose of antidiabetic drugs.

Antigout agents (probenecid, sulfinpyrazone and allopurinol). The simultaneous use of ACE inhibitors and allopurinol increases the risk of kidney damage and may lead to an increased risk of leukopenia.

It may be necessary to adjust the dose of uricosuric agents because hydrochlorothiazide may increase serum uric acid levels. It may be necessary to increase the dose of probenecid or sulfinpyrazone. With the simultaneous use of thiazides, an increase in the frequency of hypersensitivity reactions to allopurinol is possible.

Cyclosporine. The simultaneous use of ACE inhibitors and cyclosporine increases the risk of kidney damage and hyperkalemia.

Lovastatin. The simultaneous use of ACE inhibitors and lovastatin increases the risk of hyperkalemia.

Cytostatics, immunosuppressants, procainamide. Simultaneous use with ACE inhibitors may lead to an increased risk of leukopenia.

Gold. Nitritoid reactions (symptoms of vasodilation, including flushing, nausea, dizziness and arterial hypotension, which can be severe) as a result of injections of gold (for example, sodium aurothiomalate) are observed more often in patients who take lisinopril at the same time.

Amphotericin B (parenteral), carbenoxolone, corticosteroids, corticotropin (ACTH), or stimulant laxatives. Hydrochlorothiazide may exacerbate fluid and electrolyte imbalances, especially hypokalemia.

Cardiac glycosides. There is an increased risk of cardiac glycoside overdose due to thiazide-induced hypokalemia.

Cholestyramine and colestipol. May reduce or impair the absorption of hydrochlorothiazide, so Lisinopril-N should be taken at least 1:00 or 4-6 hours after taking these drugs.

Non-depolarizing muscle relaxants (eg tubocurarine). Hydrochlorothiazide may increase the effect of these drugs.

Drugs that cause torsades de pointes. Due to the risk of developing hyperkalemia, the simultaneous use of hydrochlorothiazide and drugs, the effects of which are influenced by changes in the level of potassium in the blood serum and which can lead to ventricular tachycardia of the “pirouette” type, should be carried out with caution.

Periodic monitoring of serum potassium levels and ECG examination is recommended if hydrochlorothiazide is taken concomitantly with drugs whose effects are influenced by changes in serum potassium levels and with the following drugs that cause polymorphic torsades de pointes (ventricular tachycardia), including including some antiarrhythmic drugs such as:

• Class Ia antiarrhythmics (eg, quinidine, hydroquinidine, disopyramide)

• Class III antiarrhythmics (eg, amiodarone, sotalol, dofetilide, ibutilide)

• Certain antipsychotics (eg, thioridazine, chlorpromazine, levomepromazine, trifluoroperazine) ,

cyamemazine , sulpiride, sultopride, amisulpiride, tiapride, pimozide, haloperidol, droperidol)

Other drugs (eg bepridil, cisapride, difemanil, intravenous erythromycin, halofantrine, mizolastine, pentamidine, terfenadine, vincamine intravenous).

Sotalol. Thiazide-induced hypokalemia may increase the risk of sotalol-induced arrhythmias.

Lithium preparations. Lithium should not usually be given concomitantly with diuretics or ACE inhibitors. Diuretics and ACE inhibitors reduce the renal clearance of lithium and increase the risk of lithium toxicity. If, however, there is a need to prescribe this combination of drugs, the level of lithium should be carefully monitored.

Trimethoprim. The simultaneous use of ACE inhibitors and thiazides with trimethoprim increases the risk of hyperkalemia.

Corticosteroids, ACTH. Increased loss of electrolytes, especially hypokalemia.

Pressor amines (eg epinephrine (adrenaline)). It is possible to reduce the response to the action of pressor amines, but not so much as to stop their use.

Alcohol. Alcohol can enhance the hypotensive effect of any antihypertensive drugs.

Antacids. Reduce the bioavailability of ACE inhibitors.

Metformin. Use with caution, given the risk of lactic acidosis due to possible functional renal failure due to hydrochlorothiazide.

Anticholinergics (atropine, biperidene). Due to the weakening of the motility of the digestive tract and the decrease in the rate of evacuation from the stomach, the bioavailability of thiazide-type diuretics increases.

Cytotoxic agents (eg cyclophosphamide, methotrexate). Thiazides can reduce the renal excretion of cytotoxic drugs and increase their myelosuppressive effect.

Methyldopa. Isolated cases of hemolytic anemia have been reported with the simultaneous use of hydrochlorothiazide and methyldopa.

Effects on laboratory results. Through the effect on calcium metabolism, thiazides can affect the results of assessing the function of the parathyroid glands.

Carbamazepine. Given the risk of symptomatic hyponatremia, clinical and biological monitoring is necessary.

Iodine-containing contrast agents. In the case of diuretic-induced dehydration, the risk of developing acute renal failure increases, mainly with the use of high doses of iodine-containing contrast agents. Patients require rehydration prior to administration of iodine-containing drugs.

β-blockers and diazoxide. The simultaneous use of thiazide diuretics, including hydrochlorothiazide, with β-blockers may increase the risk of hyperglycemia. Thiazide diuretics, including hydrochlorothiazide, may enhance the hyperglycemic effect of diaxoside.

Amantadine. Thiazides, including hydrochlorothiazide, may increase the risk of side effects of amantadine.

application features

Non-melanoma skin cancer.

An increased risk of non-melanoma skin cancer (NMSC) with increasing cumulative dose of HCTZ was found in two pharmacoepidemiological studies. The photosensitivity effect of HCTZ may be a mechanism for the development of this pathology.

Patients taking HCTZ alone or in combination with other drugs should be informed of the risk of developing NMSC, especially with long-term use, of the need to regularly examine the skin and immediately inform the doctor about new lesions or any suspicious growths on the skin, changes in skin lesions or moles.

To reduce the risk of developing skin cancer, patients should be informed about possible preventive measures, such as limiting exposure to sunlight and UV radiation, and, if exposed, about the need for adequate skin protection. It is necessary to examine suspicious skin lesions as soon as possible, including histological examination of biopsy material.

Patients with prior NMSC may also need to review HCTZ.

Double blockade of renin-angiotensin-(RAAS).

Simultaneous use of ACE inhibitors, angiotensin II receptor blockers or aliskiren is associated with an increased risk of arterial hypotension, hyperkalemia and impaired renal function (including acute renal failure).

If dual blockade therapy is absolutely necessary, it should be done only under specialist supervision and with close monitoring of renal function, electrolyte levels, and blood pressure at all times. ACE inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.

Arterial hypotension and disturbance of water and electrolyte balance.

As with any other antihypertensive therapy, some patients may develop hypotension.

In patients with arterial hypertension, the development of a hypotensive state is more likely with a lack of fluid, for example, during diuretic therapy, a salt-restricted diet, dialysis, diarrhea or vomiting, or in severe renin-dependent hypertension (see Sections “Interaction with other drugs and other types of interactions” and “Adverse Reactions”). Symptomatic hypotension has also been observed in patients with heart failure with or without renal failure.

This condition is more likely in patients with severe heart failure due to high doses of loop diuretics, hyponatremia, or functional renal failure.

Patients at risk of developing symptomatic hypotension at the start of therapy and during dose adjustments should be closely monitored.

In these patients, serum electrolyte levels should be measured at regular intervals.

Particular attention should be paid to the treatment of patients with ischemic heart disease or cerebrovascular disease, since an excessive decrease in blood pressure can lead to myocardial infarction or stroke.

If hypotension develops, the patient should be placed on their back and, if necessary, infused with saline. A transient hypotensive response is not a contraindication to continued therapy. After the restoration of effective blood volume and blood pressure, it is possible to restore therapy with a reduced dose or the use of one of the components of the drug separately.

Patients should be monitored appropriately to detect clinical signs of fluid-salt imbalance (eg, hypovolemia, hyponatremia, hypochloremic alkalosis, hypomagnesemia, or hypokalemia) that may develop with concomitant diarrhea or vomiting. In the warm season, patients with edema may experience hyponatremia due to blood thinning. If possible, eliminate hypovolemia and / or decrease in the volume of interstitial fluid before starting treatment with lisinopril and carefully monitor the effect of the initial dose on blood pressure. In the event of an acute myocardial infarction, lisinopril should not be used if treatment with vasodilators may worsen the patient’s hemodynamic status (for example, if systolic blood pressure is 100 mm Hg. Art.

Aortic and mitral valve stenosis / hypertrophic cardiomyopathy.

As with other ACE inhibitors, lisinopril should be used with caution in patients with left ventricular outflow tract obstruction. If the obstruction is hemodynamically significant, then taking Lisinopril-N is contraindicated (see Section “Contraindications”).

Impaired kidney function.

Thiazides are not suitable for use in patients with renal insufficiency, they are ineffective at CC 30 ml / min or below (severe renal insufficiency).

Lisinopril-N should not be administered to patients with mild or moderate renal insufficiency (creatinine clearance > 30 ml/min to <80 ml/min) until it has been established by titration of the individual components that the patient needs exactly the same doses as in the combined tablet.

In case of impaired renal function (creatinine clearance <80 ml / min), the initial dose of lisinopril should be selected depending on the indicators of creatinine clearance and on the clinical response to treatment. For such patients, continuous monitoring of the concentration of potassium and creatinine in the blood is recommended. In patients with heart failure, arterial hypotension that occurs after the start of therapy with ACE inhibitors can lead to impaired renal function. Acute renal failure has been reported, which in such cases is usually reversible.

In some patients with unilateral or bilateral renal artery stenosis or stenosis of the artery to a solitary kidney, treated with ACE inhibitors, an increase in serum urea and creatinine was observed, usually reversible after discontinuation of therapy. The likelihood of developing this condition is higher in patients with renal insufficiency. If there is also renovascular hypertension, there is an increased risk of severe hypotension and renal failure. Treatment of such patients should be started at low doses under close medical supervision, and careful dose titration is necessary. Since diuretic treatment may contribute to the development of the above situations, during the first few weeks of therapy
Lisinopril-N should monitor renal function.

Some patients with arterial hypertension without a history of kidney disease, with the simultaneous use of lisinopril and a diuretic, developed, as a rule, a slight transient increase in the concentration of urea and serum creatinine. If this occurs during therapy with Lisinopril-N, you should stop taking the combination drug. The resumption of therapy is possible after a dose reduction or one of the components of the drug separately.

After a kidney transplant.

Since there are no data on the use of lisinopril in patients after kidney transplantation, the use of the drug in this group of patients is not recommended.

Hemodialysis patients.

The use of Lisinopril-N is not indicated in patients on hemodialysis for renal failure.

Anaphylactic reactions in patients on hemodialysis.

A high risk of anaphylactic reactions has been reported in patients undergoing hemodialysis through membranes with high hydraulic permeability (e.g. AN 69) with simultaneous therapy with ACE inhibitors. For such patients, the use of a different type of dialysis membrane or the appointment of a different group of antihypertensive drugs should be considered.

Liver diseases, liver failure.

Very rarely, ACE inhibitors have been associated with a syndrome that begins with cholestatic jaundice and progresses to fulminant necrosis, sometimes fatal. The mechanism of this syndrome is unclear. Patients who develop jaundice or have a pronounced increase in liver enzymes while taking the drug should stop taking Lisinopril-N and be under appropriate control.

Thiazides, including hydrochlorothiazide, should be used with caution in patients with impaired liver function or advanced liver disease, since the drug can cause intrahepatic cholestasis, and even minimal changes in the water-salt balance can provoke the development of hepatic coma.

Surgery / Anesthesia.

In patients undergoing major surgery or during anesthesia with drugs that cause hypotension, lisinopril may additionally block the formation of angiotensin II with compensatory renin release. If the development of arterial hypotension is considered a consequence of this mechanism, it can be eliminated by introducing a large amount of fluid.

Metabolic and endocrine effects.

It is known that the simultaneous administration of ACE inhibitors and antidiabetic drugs (insulin, oral antidiabetic drugs) can cause an increase in blood glucose concentration and reduce the risk of hypoglycemia. This phenomenon is more likely to develop during the first weeks of combination therapy and in case of renal insufficiency.

Thiazide therapy may reduce glucose tolerance. Dosage adjustment of antidiabetic drugs, including insulin, may be required. Thiazides may reduce urinary calcium excretion and may cause an abrupt and slight increase in serum calcium. Severe hyperkalemia may be a sign of latent hyperparathyroidism. You should stop taking thiazide diuretics for tests to assess the function of the parathyroid glands. An increase in the concentration of cholesterol and triglycerides may be associated with thiazide diuretic therapy.

Thiazide therapy may precipitate hyperuricemia and/or gout in some patients. However, lisinopril can increase the level of uric acid in the urine and thereby weaken the hyperuricemic effect of hydrochlorothiazide.

Hypersensitivity / angioedema.

Isolated cases of angioedema of the face, extremities, lips, tongue, vocal cords and/or larynx have been reported in patients treated with ACE inhibitors, including lisinopril. These phenomena can develop at any stage of treatment. In this case, lisinopril should be discontinued immediately and appropriate supervision instituted to ensure complete resolution of symptoms before the patient is discharged. Even when there is only swelling of the tongue without the development of respiratory failure, long-term monitoring of the patient may be required, since antihistamine and corticosteroid therapy may not be enough.